Animal models for enterovirus 71: Mechanisms, immunity, and applications

Enterovirus 71 (EV-A71) is a leading cause of hand, foot, and mouth disease (HFMD) in young children and is associated with a risk of severe neurological complications. Although inactivated vaccines ae available, their limited cross-protective efficacy and the lack of approved antiviral treatments highlight the need for robust animal models to investigate viral pathogenesis and evaluate therapeutic interventions. This review provides a comprehensive overview of current EV-A71 animal models, particularly focusing on murine systems, and their applications in understanding disease mechanisms, supporting vaccine development, and developing antiviral strategies. The use of various EV-A71 strains, including clinical isolates, mouse-adapted strains, and infectious clones, in conjunction with rodent models such as BALB/c, ICR, and C57BL/6 neonatal mice, is examined. Additionally, transgenic, immunodeficient, and hybrid mouse models are also discussed for their ability to simulate key clinical features of infection, such as neurotropism, paralysis, and mortality. These models are indispensable for advancing therapeutic and vaccine research in pediatric infectious diseases.